Comparing transcriptional responses to Fusarium crown rot in wheat and barley identified an important relationship between disease resistance and drought tolerance.

BACKGROUND: Fusarium crown rot (FCR) is a chronic disease in cereal production worldwide. The impact of this disease is highly environmentally dependant and significant yield losses occur mainly in drought-affected crops. RESULTS: In the study reported here, we evaluated possible relationships between genes conferring FCR resistance and drought tolerance using two approaches. The first approach studied FCR induced differentially expressed genes (DEGs) targeting two barley and one wheat loci against a panel of genes curated from the literature based on known functions in drought tolerance. Of the 149 curated genes, 61.0% were responsive to FCR infection across the three loci. The second approach was a comparison of the global DEGs induced by FCR infection with the global transcriptomic responses under drought in wheat. This analysis found that approximately 48.0% of the DEGs detected one week following drought treatment and 74.4% of the DEGs detected three weeks following drought treatment were also differentially expressed between the susceptible and resistant isolines under FCR infection at one or more timepoints. As for the results from the first approach, the vast majority of common DEGs were downregulated under drought and expressed more highly in the resistant isoline than the sensitive isoline under FCR infection. CONCLUSIONS: Results from this study suggest that the resistant isoline in wheat was experiencing less drought stress, which could contribute to the stronger defence response than the sensitive isoline. However, most of the genes induced by drought stress in barley were more highly expressed in the susceptible isolines than the resistant isolines under infection, indicating that genes conferring drought tolerance and FCR resistance may interact differently between these two crop species. Nevertheless, the strong relationship between FCR resistance and drought responsiveness provides further evidence indicating the possibility to enhance FCR resistance by manipulating genes conferring drought tolerance.

Analysis of soluble or titanium dioxide derived titanium levels in human whole blood: consensus from an inter-laboratory comparison.

Exposure to titanium (Ti), via the ingestion of pigment grade Ti dioxide (TiO2), is commonplace for westernised populations. It may also occur as a consequence of metal ion leaching in subjects bearing Ti-containing implants. Accurate exposure analysis requires fit-for-purpose analytical methodology, especially for true measures of baseline levels. Inductively coupled plasma (ICP) techniques are, mainly, now used for bio-analysis of Ti. Since whole blood reference materials, certified for natural low levels of Ti, are not currently available, we undertook an inter-laboratory comparison of pooled human blood from fasted volunteers ±low level (+∼2.5 µg L-1) or high level (+10-20 µg L-1) spikes of soluble Ti or TiO2 particles. Seven established laboratories were enrolled to analyse the samples using ICP based techniques, which included at least one of ICP optical emission spectrometry (ICP-OES), high resolution ICP mass spectrometry (HR-ICP-MS), triple quadrupole ICP-MS (ICP-MS/MS) or single quadrupole ICP-MS (SQ-ICP-MS). Five laboratories diluted the blood for analysis whilst two performed acid digestion. Overall, we showed that the laboratories could, mostly, quantitatively detect modest levels of spiked Ti in blood. Markedly varying levels of Ti, however, were reported for the same baseline pooled sample (0.4-24.6 µg L-1) and, in this study, specificity was poor for SQ-ICP-MS. Digestion of samples caused sample contamination compromising limits of detection and accuracy, whilst simple dilution had no such problem, and remained linear in response for spikes with ionic and TiO2 particles. We conclude that measuring baseline levels of Ti in whole blood is challenging but should be readily achievable down to 0.5-1.5 µg L-1, if sample preparation avoids contamination and instrument techniques are used that negate polyatomic or isobaric interferences from the sample matrix. We also remind those relying upon Ti bio-analytical data for their experimental outcomes that (a) spiking and recovery experiments provide information only on linearity of detection but not at all on accuracy as this will not detect constant positive errors and that (b) biological standard materials for Ti generally contain high levels of the analyte and tend to mask baseline analytical errors. Caution may be required in interpreting the findings of some published Ti/TiO2 bio-exposure studies.

Positive association between serum silicon levels and bone mineral density in female rats following oral silicon supplementation with monomethylsilanetriol.

UNLABELLED: Observational (epidemiological) studies suggest the positive association between dietary silicon intake and bone mineral density may be mediated by circulating estradiol level. Here, we report the results of a silicon supplementation study in rats that strongly support these observations and suggest an interaction between silicon and estradiol. INTRODUCTION: Epidemiological studies report strong positive associations between dietary silicon (Si) intake and bone mineral density (BMD) in premenopausal women and indicate that the association may be mediated by estradiol. We have tested this possibility in a mixed-gender rodent intervention study. METHODS: Tissue samples were obtained from three groups of 20-week-old Sprague Dawley rats (five males and five females per group) that had been supplemented ad libitum for 90 days in their drinking water with (i) <0.1 mg Si/L (vehicle control), (ii) 115 mg Si/L (moderate dose) or (iii) 575 mg Si/L (high dose). All rats received conventional laboratory feed, whilst supplemental Si was in the form of monomethylsilanetriol, increasing dietary Si intakes by 18 and 99 %, for the moderate- and high-dose groups, respectively. RESULTS: Fasting serum and tissue Si concentrations were increased with Si supplementation (p < 0.05), regardless of gender. However, only for female rats was there (i) a trend for a dose-responsive increase in serum osteocalcin concentration with Si intervention and (ii) strong significant associations between serum Si concentrations and measures of bone quality (p < 0.01). Correlations were weaker or insignificant for tibia Si levels and absent for other serum or tibia elemental concentrations and bone quality measures. CONCLUSIONS: Our findings support the epidemiological observations that dietary Si positively impacts BMD in younger females, and this may be due to a Si-estradiol interaction. Moreover, these data suggest that the Si effect is mediated systemically, rather than through its incorporation into bone.

Treatment of vulvar lichen sclerosus with topical corticosteroids in children: a study of 72 children.

Treatment of vulvar lichen sclerosus (VLS) in children by topical corticosteroids gives control of symptoms and some resolution of physical signs, but large studies are limited. We report the largest study of 72 prepubertal girls with VLS, 62 of whom were prospectively treated with daily application of an ultrapotent topical corticosteroid (UPTC), clobetasol propionate 0.05% ointment, for 3 months, with a follow-up period of 4-8 years [the remaining 10 patients responded to mild to moderate potency topical corticosteroids (MPTCs)]. The results were compared with a retrospective study of 31 prepubertal girls with VLS treated with MPTCs. MPTCs led to symptom clearance in 32.2% of patients, whereas UPTC led to symptom clearance in 72.6% of patients. Improvement in clinical signs following UPTC occurred in 90.3% of children at 3 months, with total resolution of clinical signs occurring in 29.2% at the 4-year follow-up or at puberty. No serious adverse effects occurred with UPTC treatment. In children with VLS, UPTCs relieve symptoms, resolve signs and possibly prevent scarring. UPTCs should therefore be the treatment of choice for VLS in children.

Surveillance of Patients with Metal-on-Metal Hip Resurfacing and Total Hip Prostheses: A Prospective Cohort Study to Investigate the Relationship Between Blood Metal Ion Levels and Implant Failure.

BACKGROUND: We designed a prospective, single-center study to assess whether blood metal ion levels could predict implant failure in patients managed with unilateral metal-on-metal hip resurfacing or total hip arthroplasty. METHODS: Five hundred and ninety-seven patients who had received unilateral Articular Surface Replacement prostheses at least twelve months earlier were recruited. Blood metal ion levels were compared between the group of patients with failed implants and the group with non-failed implants. Implant failure was defined as prostheses associated with revision, an intention to revise, or poor patient-reported hip function (Oxford Hip Score, <31 of 48). Specificity, sensitivity, area under the curve, positive and negative predictive values, and odds ratios were calculated. Logistic regression analysis was used to identify other risk factors for implant failure. RESULTS: Patients with failed arthroplasty had significantly higher blood cobalt and chromium ion levels than did patients with non-failed arthroplasty (p < 0.01). Blood cobalt ion levels were disproportionately raised in patients with failed total hip arthroplasty (8.2 µg/L) compared with patients with failed hip resurfacing (2.5 µg/L) (p = 0.018). Blood chromium ion levels were not significantly different in patients with failed total hip arthroplasty and failed hip resurfacing (p = 0.058). The maximum value of either metal ion had good discriminant ability to predict implant failure (area under the curve, 0.76). A 7-µg/L cutoff had a positive predictive value of 0.75 (95% confidence interval, 0.66 to 0.82) and a negative predictive value of 0.82 (95% confidence interval, 0.78 to 0.86). In patients managed with total hip arthroplasty, for each increase of 1 µg/L there was a 23% (p < 0.001) increase in the odds of them being in the failed group. For patients managed with hip resurfacing, the increase in odds was 5% (p < 0.001). CONCLUSIONS: Raised levels of blood metal ions were associated with failed metal-on-metal hip resurfacings and total hip arthroplasties. A threshold level of 7 µg/L had inadequate sensitivity to be used in isolation as a screening test for implant failure, but it provided nearly optimal misclassification rates. No level had a perfect positive predictive value, and so we discourage surgeons from performing revision surgery based on blood metal ion levels alone. Levels of cobalt ions were raised out of proportion to levels of chromium ions in failed total hip arthroplasty and may reflect a different mechanism for metal ion generation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Circulating levels of cobalt and chromium from metal-on-metal hip replacement are associated with CD8+ T-cell lymphopenia.

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Laboratory-defined T-cell lymphopenia was present in 13 patients (15%) (CD8(+) lymphopenia) and 11 patients (13%) (CD3(+) lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8(+) lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

Cup inclination angle of greater than 50 degrees increases whole blood concentrations of cobalt and chromium ions after metal-on-metal hip resurfacing.

A cup inclination angle greater than 45 degrees is associated with increased wear rates of metal on polyethylene (MOP) hip replacements. The same maybe true for metal on metal (MOM) hips yet this has not been clearly shown. We measured the acetabular inclination angle from plain radiographs, and whole blood metal ion levels using Inductively Coupled Plasma Mass Spectrometry of 26 patients (mean Harris Hip Score 94 and mean time post op of 22 months) with Birmingham Hip Resurfacings. We identified a threshold level of 50 degrees cup inclination. Below this threshold, the mean whole blood cobalt and chromium were 1.6 ppb and 1.88 ppb respectively; above this threshold, the mean blood cobalt and chromium were 4.45 ppb and 4.3 ppb respectively. These differences were significant cobalt (p<0.01) and chromium (p=0.01). All patients above the threshold had metal levels greater than any of the patients below the threshold. For 14 patients, who returned one year later for a repeat blood metal level measurement, cobalt and chromium levels were very similar. The effect of an acetabular inclination angle of greater than 50 degrees on wear rates of MOM hips, as measured through blood metal ion levels, appears to be similar to that seen with MOP hips. Additionally, our new analytical methods may allow blood metal levels to be used as a realistic biomarker of in vivo wear rate of MOM hips. The implication is that metal levels can be minimised with optimal orientation of the acetabular component.

Phenotype of exogenous microparticle-containing pigment cells of the human Peyer's patch in inflamed and normal ileum.

OBJECTIVES: Pigmented cells, that contain inert, submicron-sized dietary particles, are a consistent feature of the base of human Peyer's patches (PP). We aimed (i) to phenotype these intestinal pigment cells (PC) in archival tissue specimens and (ii) to establish whether PC phenotype is altered in inflammatory conditions, especially Crohn's disease (CD). METHODS: PCs contained within PP were identified by routine haematoxylin and eosin (H&E) staining and dark field microscopy of archival ileal sections for: adenocarcinoma (n=16), colonic CD (n=23), non-CD colitis (n=10). Paraffin-embedded serial sections were graded for microscopic inflammation and then investigated immunohistochemically with antibodies against CD68, MAC387, CD14, CD11b, CD15, CD1a, S100, HLA-DR, CD86 and Cathepsin D. Analyses were by light and confocal microscopies. RESULTS: The majority of PCs were CD68 positive (circa 80%) with a minority (circa 20%) staining for MAC387. Microparticles were mainly identified within cathepsin D negative lysosomal compartments. Histological inflammatory grade and disease type had no influence on cell phenotype. CONCLUSIONS: The microparticle-containing PCs of the PP base are mainly mature macrophages (CD68) of low metabolic and immunological activity. There is no evidence of differential PC phenotype or activation in differing disease states, including CD.

Dietary microparticles implicated in Crohn's disease can impair macrophage phagocytic activity and act as adjuvants in the presence of bacterial stimuli.

OBJECTIVE AND DESIGN: Western diets regularly expose the gastrointestinal tract (GI) to large quantities ( > 10(12)/day) of man-made, submicron-sized, particles derived from food additives and excipients. These are taken up by M cells, accumulate in gut macrophages, and may influence the aetiology of inflammatory bowel diseases (IBD). MATERIALS: We investigated the effects of common dietary microparticles on the function of macrophages from healthy donors or active Crohn's disease (CD) patients. METHODS: Macrophages were incubated for 24 h with microparticles before being assayed for cytokine production and phagocytic activity. RESULTS: Microparticles alone were non-stimulatory but, in the presence of bacterial antigens such as LPS, they could act as adjuvants to induce potent cytokine responses. Uptake of high concentrations of microparticles also impaired macrophage phagocytic capacity - but not their ability - to take up 2microM fluorescent beads. CONCLUSIONS: While dietary microparticles alone have limited effects on basic macrophage functions, their ability to act as adjuvants could aggravate ongoing inflammatory responses towards bacterial antigens in the GI tract.

Peripheral blood mononuclear cell proliferative responses to soluble and particulate heat shock protein 65 in health and inflammatory bowel disease.

OBJECTIVES: The aims of this study were to determine, in peripheral blood mononuclear cells (PBMC), whether particulate antigen triggers (i) an amplified cell proliferative response compared to soluble antigen and (ii) a dysfunctional response in cells derived from patients with chronic inflammation and specifically in those with inflammatory bowel disease (IBD). SUBJECTS: Healthy volunteers (n = 17), inflammatory controls (n = 8) and patients with IBD (n = 17) were recruited from St Thomas' and Guys' Hospital, London, UK. METHODS: Following optimisation of experimental conditions (0.1-10.0 mug/ml antigen), PBMC were stimulated with (i) 10.0 mug/ml recombinant soluble heat shock protein 65 (hsp 65) and (ii) 1.0 and 10.0 mug/ml hsp 65 conjugated to microparticles (0.5 mum diameter). PBMC proliferative responses were measured by (3)H-Thymidine incorporation at day 5 and results compared between groups using unpaired t-test. RESULTS: Conjugation to microparticles of low dose hsp 65 significantly increased overall proliferative responses by 2-11 fold compared to soluble antigen alone (p < 0.05). However, no specific PBMC proliferative dysregulation was noted in cells from subjects with IBD. CONCLUSIONS: Low dose antigen, in microparticulate form, leads to amplified cell proliferation in primary human cells, as showed previously in cell lines and animal studies. However there is no abnormal proliferative response in cells from subjects with IBD.

Immunolocalization of duodenal cytochrome B: a relationship with circulating markers of iron status.

BACKGROUND: The brush border ferric reductase (Dcytb) is critical for the absorption of dietary iron and appears to be expressed on the duodenal enterocyte brush border. The Dcytb expression is increased in severe iron-deficient anaemia, but the situation in a more typical mild iron deficiency is unclear. This study investigated Dcytb expression in patients with normal iron status or mild iron deficiency and its relationships with enterocyte iron status. MATERIALS AND METHODS: Duodenal biopsy specimens and blood samples were obtained from 32 patients undergoing routine upper gastrointestinal endoscopy. Twenty-three specimens (six iron-deficient and 17 iron-replete) were processed for light-microscopy (LM) and for immunohistochemistry with antibodies against Dcytb and heavy/light chain ferritin subunits. The nine remaining biopsies (three iron-deficient and six iron-replete) were processed for electron microscopy (EM). Immunolocalization of Dcytb and intracellular ferritin was performed with appropriate primary antibodies followed by 10-nm gold conjugate labels. RESULTS: The LM process showed a strong negative correlation between immunolabelling intensity of Dcytb on the enterocyte brush border and serum iron saturation (P < 0.001), but only a weak negative correlation between this antigen and haemoglobin (P = 0.08) or serum ferritin concentrations (P = 0.4). EM confirmed anti-Dcytb preferential labelling of microvilli rather than enterocyte cytoplasm (P = 0.001), but preferential antiferritin labelling of cytoplasm (P < 0.02). There was no correlation with enterocyte cytoplasmic ferritin labelling (i.e. enterocyte iron status and Dcytb expression). CONCLUSIONS: Enterocyte Dcytb brush border expression is increased even in mild iron deficiency and may be related to serum iron saturation. The lack of correlation with enterocyte ferritin expression deserves further study with direct measurement of intracellular iron.

Moderate alcohol consumption and increased bone mineral density: potential ethanol and non-ethanol mechanisms.

Mounting epidemiological evidence indicates an association between the moderate ingestion of alcoholic beverages and higher bone mineral density (v. abstainers). More limited findings provide some evidence for translation of this association into reduced fracture risk, but further studies are required. Here, these data are reviewed and caveats in their assimilation, comparison and interpretation as well as in the use and application of bone health indices are discussed. Whilst it is concluded that evidence is now strong for the moderate alcohol-bone health association, at least in relation to bone mineral density, mechanisms are less clear. Both ethanol and non-ethanol components have been implicated as factors that positively affect bone health in the light of moderate consumption of alcoholic beverages, and four particular areas are discussed. First, recent findings suggest that moderate ethanol consumption acutely inhibits bone resorption, in a non-parathyroid hormone- and non-calcitonin-dependent fashion, which can only partly be attributed to an energy effect. Second, critical review of the literature does not support a role for moderate ethanol consumption affecting oestrogen status and leading to a knock-on effect on bone. Third, Si is present at high levels in certain alcoholic beverages, especially beer, and may have a measurable role in promoting bone formation. Fourth, a large body of work indicates that phytochemicals (e.g. polyphenols) from alcoholic beverages could influence bone health, but human data are lacking. With further work it is hoped to be able to model epidemiological observations and provide a clear pathway between the magnitude of association and the relative contribution of these mechanisms for the major classes of alcoholic beverage.

The association between metal ions from hip resurfacing and reduced T-cell counts.

We have studied the relationship between metal ion levels and lymphocyte counts in patients with metal-on-metal hip resurfacings. Peripheral blood samples were analysed for lymphocyte subtypes and whole blood cobalt and chromium ion levels in 68 patients (34 with metal-on-metal hip resurfacings and 34 with standard metal-on-polyethylene total hip replacements). All hip components were radiologically well-fixed and the patients were asymptomatic. Cobalt and chromium levels were significantly elevated in the patients with metal-on-metal hip resurfacings, compared with the patients with standard metal-on-polyethylene designs (p < 0.0001). There was a statistically significant decrease in the level of CD8(+) cells (T-cytotoxic/suppressor) (p = 0.005) in the metal-on-metal hip resurfacing group. A threshold level of blood cobalt and chromium ions was associated with reduced CD8(+) T-cell counts. We have no evidence that our patients suffered as a result of this reduced level of CD8(+) T-cells.

Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P.

OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.

Effect of humic acid on water chemistry, bioavailability and toxicity of aluminium in the freshwater snail, Lymnaea stagnalis, at neutral pH.

The influence of humic acid on the water chemistry of environmentally relevant concentrations of Al at neutral pH was studied, together with its effect on the bioavailability and toxicity of Al in Lymnaea stagnalis. Humic acid significantly reduced the loss of Al from the water and increased the fraction of filterable Al, although this was a relatively small fraction of total Al. Filterable Al concentration in the presence or absence of humic acid was independent of initial Al concentration. Humic acid only partly reduced toxicity, as observed by a reduction in behavioural suppression, and had no effect on the level of Al accumulated in tissues. These results suggest that humic acid maintains Al in a colloidal form that is bioavailable to L. stagnalis. However, these colloidal Al-humic acid species were less toxic since behavioural toxicity was reduced. Humic acid may play an important role in limiting the toxicity of Al to freshwater organisms.

A provisional database for the silicon content of foods in the United Kingdom.

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma-optical emission spectrometry following microwave-assisted digestion with nitric acid and H(2)O(2). The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.

Dietary silicon intake in post-menopausal women.

Si has been suggested as an essential element, and may be important in optimal bone, skin and cardiovascular health. However, there are few estimates of dietary Si intakes in man, especially in a UK population. Following the development of a UK food composition database for Si, the aim of the present study was to investigate dietary intakes of Si amongst healthy women aged over 60 years and to identify important food sources of Si in their diet. Healthy, post-menopausal female subjects (>60 years of age; n 209) were recruited from the general population around Dundee, Scotland as part of an unrelated randomised controlled intervention study where dietary intake was assessed using a self-administered, semi-quantitative food-frequency questionnaire at five time-points over a 2-year period. Food composition data on the Si content of UK foods was used to determine the Si content of food items on the food-frequency questionnaire. Mean Si intake was 18.6 (sd 4.6) mg and did not vary significantly across the 2 years of investigation. Cereals provided the greatest amount of Si in the diet (about 30 %), followed by fruit, beverages (hot, cold and alcoholic beverages combined) and vegetables; together these foods provided over 75 % about Si intake. Si intakes in the UK appear consistent with those reported previously for elderly women in Western populations, but lower than those reported for younger women or for men.

Interferon-gamma polymorphisms correlate with duration of survival in pancreatic cancer.

Despite progress in diagnosis and staging, pancreatic cancer still has a poor prognosis and it remains difficult to predict duration of survival in advanced pancreatic cancer. Nutritional decline, or cachexia, is a contributory factor to decreased survival in advanced pancreatic carcinoma, and it has been demonstrated that proinflammatory cytokines give rise to cachexia. Interferon (IFN)-gamma is a proinflammatory cytokine whose administration increases survival outcomes in a variety of cancers. The human IFN-gamma gene has a variable length CA-repeat sequence, the length that has been shown to influence IFN-gamma production. The current study was performed to ascertain whether polymorphisms of the IFN-gamma gene would influence survival of individuals with advanced pancreatic cancer. The study demonstrated that the presence of allele 2 (12 CA repeats) was consistently associated with increased duration of survival after confirmation of nonresectable pancreatic carcinoma. We therefore propose that the presence of allele 2 may be a useful marker for patient outcome.

Role of exogenous and endogenous silicon in ameliorating behavioural responses to aluminium in a freshwater snail.

Aluminium accumulation by the freshwater snail Lymnaea stagnalis is correlated with behavioural depression which is ameliorated by addition of orthosilicic acid. We hypothesised that Si is relocated to the digestive gland in response to Al, leading to the formation of non-toxic hydroxyaluminosilicates (HAS). Exposure to 500 microg l(-1) Al for 30 days was associated with an initial period of behavioural depression, followed by apparent tolerance and subsequent depression, suggesting saturation of the cellular detoxification pathway during prolonged exposure. Exogenous Si (7.77 mg l(-1)) completely ameliorated all behavioural effects of Al but did not prevent its accumulation. In the presence of added Al, significantly more of this Si was accumulated by the tissues, compared to controls and snails exposed to Si alone. In snails exposed to Al plus Si, Al and Si concentrations were significantly correlated, with a ratio around 3:1 Al:Si, consistent with the presence of the non-toxic HAS protoimogolite.